With higher demands for personalized medicine and smart, programmable drug delivery systems, more flexible and smaller micropumps will be increasingly called upon by clinicians and bioengineering researchers. These smaller and more controllable micropumps will be essential for delivering experimental drugs for many systems in the body, including sensorineural, visual, cardiac, brain and so on. In the present proposal advanced micro-, drug- delivery systems will be developed and tested, initially, for delivery to the inner ear for hearing loss, deafness and vestibular biotherapeutic applications. More specifically, permanent hearing loss and deafness are major communicative disorders, affecting over 10% of the US population, and comprising the number one neurodegenerative problem and communication disorder of our aged population. This grant proposal consists of a set of discrete but connected bioengineering disciplines organized to (1) to develop novel micropumps for drug delivery, (2) determine pump parameters and functional characteristics with a unique interplay of quantitative modeling and CT scan biomedical imaging, and (3) test the new micropumps in vivo by infusing a contrast agent into the cochlea for quantitative comparison to syringe pump infusions, and then infusion of salicylate weekly over a one month time period to demonstrate utility of the technology for programmable, more chronic infusions. Engineering-oriented strategies are employed in a common set of specific aims building on key initial progress and preliminary results concerning application of bioengineering techniques to in vivo drug delivery. Notably, we have already demonstrated that key elements of the implantable micropump can be fabricated with microsystems technologies; that fluid and solute flow through the mouse cochlea can be quantitatively modeled and visualized with state-of-the-art CT biomedical imaging; and that we can reliably deliver compounds to the round window membrane niche of the mouse for intracochlear drug delivery applications. Although translational interventions lie close on the horizon, several additional aspects of this line of research need to be accomplished before such undertakings will be clinically successful for clinical trials in children and adults. So, in the present proposal, we propose a set of synergistically related microsystems, bioengineering, biomedical imaging, modeling, and animal physiology experiments attacking these remaining issues to ensure the eventual bench-to-bedside success that is needed.